Protein Structure

Amino Acid Review

• Recognizable Amino Acids: Students must be able to recognize the R-groups of: Leucine, Phenylalanine, Cysteine, Serine, and Lysine.

• Basic Amino Carboxylic Acid Structure:

  • Students must be able to draw this basic structure.

  • Orientation: The amino group ($NH_2$) is always drawn on the left (N-terminus), and the carboxylic acid group ($COOH$) is always on the right (C-terminus).

  • Reason: Ribosomes synthesize peptides starting with the amino group and ending with the carboxylic acid group, hence the N-to-C, left-to-right convention.

  • Physiological pH:

    • Amino Group: At physiological pH, it is protonated ($NH_3^+$).

    • Carboxylic Acid Group: At physiological pH, it is deprotonated ($COO^-$).

    • Central Carbon ($\alpha$-carbon): Bears a hydrogen and the unique R-group.

• Classifying R-Groups: Expect to classify amino acids based on their R-groups.

  • Nonpolar R-groups:

    • Examples: Alanine (methyl), Leucine, Phenylalanine.

    • Characteristics: Composed primarily of carbons and hydrogens; equal electron sharing; no partial charges.

    • Interactions: Interact with other nonpolar R-groups (hydrophobic interactions).

  • Polar R-groups:

    • Examples: Serine (hydroxyl group), Cysteine (sulfhydryl group).

    • Interactions: Interact with other polar R-groups, water (in aqueous environments), and phospholipid head groups in membranes.

    • Aqueous vs. Liquid Clarification:

      • Liquid: Refers to the state of matter.

      • Aqueous: A solution where water is the solvent (e.g., oil is liquid but not aqueous). Polar R-groups readily interact with water in an aqueous environment.

  • Electrically Charged R-groups:

    • Examples: Lysine (has a full positive charge, basic). Acidic amino acids have full negative charges.

    • Interactions: Positively charged R-groups interact with negatively charged R-groups via ionic bonds.

Peptide Bonds and Protein Structure Levels

• Peptide Bond Formation: Formed via a dehydration reaction between the carboxyl group of one amino acid and the amino group of another, creating a dipeptide.

  • Dipeptide Convention: N-terminus on the left, C-terminus on the right. Each amino acid in a peptide is called a 'residue.'

• The Peptide Bond:

  • A covalent bond formed specifically between the carbon of the carboxyl group ($C=O$) and the nitrogen of the amino group ($NH$).

  • Intramolecular Force: This bond is an intramolecular force, as it exists within the same molecule.

  • Primary Protein Structure: Peptide bonds are responsible for holding together the primary structure of a protein (the linear sequence of amino acids).

• Peptide Backbone:

  • Consists of repeating Nitrogen-Carbon-Carbon (N-C-C) units.

  • If a peptide has $200$ residues, this N-C-C unit repeats $200$ times.

  • The peptide backbone is what forms the core structural elements without the R-groups.

• Secondary Protein Structure:

  • Maintained by hydrogen bonds formed between atoms in the peptide backbone.

  • These are intramolecular forces.

  • Note on Hydrogen Bonds: Hydrogen bonds can be intermolecular (between different molecules, like water) or intramolecular (within the same large molecule, like a protein).

  • Types of Secondary Structures:

    • Alpha Helix ($\alpha$-helix): A coiled, helix-like structure. Hydrogen bonds form between the carbonyl oxygen of one residue and the amino hydrogen of a residue approximately $3 - 3.5$ positions away. R-groups protrude outwards.

    • Beta Sheet ($\beta$-sheet or Beta Pleated Sheet): A flattened, accordion-folded structure. Also held by hydrogen bonds between backbone atoms, but across different, often non-adjacent, segments of the peptide backbone. R-groups project above and below the sheet.

    • Random Coil: Regions of the protein backbone that do not adopt a regular, repeating secondary structure.

• Tertiary Protein Structure:

  • The overall three-dimensional shape of a single peptide chain.

  • Maintained by various interactions between the R-groups of amino acids.

  • These are all intramolecular forces.

  • Types of R-Group Interactions:

    • Ionic Bonds: Between oppositely charged R-groups (e.g., Lysine with an acidic residue).

    • Hydrogen Bonds: Between polar R-groups.

    • Van der Waals Attractions: Weak, transient interactions occurring between all molecules but are collectively significant for nonpolar (hydrophobic) R-groups, causing them to congregate.

    • Disulfide Bridges: A strong covalent bond formed between the sulfhydryl groups ($-\text{SH}$) of two Cysteine residues. Occurs specifically in oxidative environments.

• Quaternary Protein Structure:

  • The arrangement of multiple peptide chains (subunits) interacting to form a functional protein complex.

  • Involves intermolecular interactions between R-groups of different peptides.

  • Example: Hemoglobin, a tetramer requiring four subunits ($2$ alpha, $2$ beta peptides) to function.

Protein Folding in an Aqueous Environment (e.g., Actin in Cytosol)

• Cytosol Characteristics: The cytosol is an aqueous, reducing environment.

• Actin (Globular Protein) Example:

  • Nonpolar (Hydrophobic) R-groups: Tend to be located on the inside of the protein, away from water. They interact via Van der Waals forces, effectively excluding water.

  • Polar (Hydrophilic) R-groups: Tend to be located on the outside of the protein, facing the aqueous environment. They interact with water and other polar molecules.

  • Exceptions: Hydrophobic patches or polar/ionic interactions might occur in less typical locations for specific functions.

  • Implications: Helps predict the location of different amino acids in membrane proteins.